tCho Levels Research Articles

Effects of dietary lipid and protein levels on metamorphosis, growth, metabolism and gut microbiota of tadpole (Lithobates catesbeianus)

Tadpole cultivation is a crucial step in the artificial production of bullfrogs (Lithobates catesbeiana), but its feed nutrition is poorly understood. This study examined how dietary lipid and protein levels affect metamorphosis, growth and intestinal health of tadpole. Six groups of tadpoles were fed six diets with two lipid levels (7% and 10%) and three protein levels (36%, 40% and 44%) for 70 days. The results showed that at 7% lipid level, increasing protein enhanced metamorphosis rate and mean weight of tadpoles, reaching the optimal value at 40% protein (P < 0.05). At 10% lipid level, increasing protein also improved mean weight, peaking at 40% protein. Dietary nutrition also influenced liver amino acid and lipid metabolism directly. At 7% lipid level, increasing protein significantly increased the activities of hepatic enzymes GLS, PDH, ALT, AST, etc. (P < 0.05), and up-regulated the expression of hepatic genes fas, accb, fadd6 and cpt1a involved in lipid metabolism (P < 0.05). At 10% lipid level, increasing protein also up-regulated fadd6 and cpt1a genes (P < 0.05), but down-regulated acadl gene. Meanwhile, increasing dietary lipid level elevated TG and T-CHO levels in liver. Increasing dietary protein enhanced gut microbiota richness, while increasing lipid reduced it. Moreover, different gut microbiota groups had distinct biomarkers, such as Rikenellaceae, Desulfovibrionaceae, Burkholderiales and Bacteroidales, which were related to amino acid or lipid metabolism. In summary, under the test conditions, 7% lipid and 40% protein in diet are suitable levels, which can promote metamorphosis, growth and metabolism of tadpoles, and are more economical than high-lipid and high-protein diets.

Effects of soyhulls with different particle size on the growth performance, blood indices and gut microbiota of yellow feather broilers

ABSTRACT 1. The objective of this study was to determine the effects of soyhulls with different particle sizes on the growth performance, blood indices and gut microbiota of yellow feather broilers. 2. Total of 240 healthy, one-day-old, yellow feather broilers were randomly divided into four groups, with six pen replicates within each group and ten birds per pen. The control group birds were fed the basal diet (Control). For the treatment groups, 5% soyhulls with different particle sizes were included in the basal diet. The particle size geometric mean diameters (d gw) of the soyhulls in the three treatment groups were 299.69 μm (LowPS), 489.85 μm (MediumPS) and 734.83 μm (HighPS) with geometric standard deviation (S gw) 1.75 μm, 1.62 μm and 1.67 μm, respectively. 3. Results showed that the growth performance variables and organ indices were not different among the four groups. The MediumPS group had increased TG, T-CHO, ALT, HDL-C, and GSH-PX levels and decreased T-AOC levels, whereas LowPS and HighPS groups had increased HDL-C and GSH-PX levels (p < 0.05). Microbial diversity analysis showed that the intestinal microbiota of yellow feather broilers mainly included Firmicutes and Bacteroidetes. Inclusion of 5% soyhulls with different particle size had no effect on alpha diversity indices of caecal microbiota. The HighPS group had significantly higher relative abundance of Firmicutes spp. and lower Bacteroidetes spp. compared with the LowPS and MediumPS group but this was not different from the Control group. The relative abundance of Cyanobacteria spp. was significantly higher in the HighPS group than the other three groups. LEfSe analysis showed that there were more enriched biomarker taxa in the groups with soyhulls than the control group. 4. Overall, the inclusion of soyhulls with different particle sizes had limited effects on growth performance, blood indices and caecal microbiota composition of yellow feather broilers.

Peanut-natto improved obesity of high-fat diet mice by regulating gut microbiota and lipid metabolism

Globally, the incidence of diseases such as obesity, fatty liver and hyperlipidaemia has increased drastically in recent years. This study investigated the direct treatment of obesity and its associated metabolic disorders using peanut-natto in a high-fat diet (HFD)–induced mouse model of obesity. After 6 weeks of treatment, peanut-natto significantly reduced the body and abdominal fat weight of mice with obesity, decreased the fat cell area and fat droplet accumulation in the liver and improved the colon structure by regulating the levels of intestinal lipid metabolism-related proteins such as CD36 and FATP4. Compared with the untreated HFD group, peanut-natto significantly reduced the serum levels of LDL-C, TG and T-CHO. Metagenomic analysis revealed that natto can restore the abundance of gut microbiota to a certain extent and increase the Bacteroidetes-to-Firmicutes ratio. Non-targeted metabolomics analysis indicated a metabolism disorder that was obviously improved by peanut-natto treatment via the regulation of α-linolenic acid metabolism, linoleic acid metabolism, unsaturated fatty acid biosynthesis and lipid decomposition in fat cells. These results provide a scientific basis for using peanut-natto as a new food product to prevent obesity, improve metabolic disorders and balance the intestinal microbiota.

Reduced GABA concentration in patients with white matter hyperintensities.

To investigate potential alterations of white matter hyperintensities (WMHs) on J-edited MR spectroscopy (MRS) measures of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA). Twenty-four WMHs patients and 20 healthy controls (HCs) were recruited to undergo magnetic resonance spectroscopy (MRS) scan at 3T from voxels in left centrum semiovale white matter, using the MEGA point resolved spectroscopy (MEGA-PRESS) technique with the MATLAB-based Gannet tool to estimate GABA+ co-edited macromolecule (GABA+) levels and using Tarquin software to estimate levels of glutamate + glutamine (Glx), total N-acetylaspartate (tNAA), total choline (tCho), and total creatine (tCr). Independent t-tests or Mann-Whitney U-tests were used to test group differences between WMHs and HCs. Additionally, WMHs patients were divided into mild and moderate-severe WMHs subgroup according to the Fazekas scale. Analysis of variance (ANOVA) and post-hoc tests were used among WMHs subgroups and HCs. We found there was a significant reduction in GABA+ levels (p = 0.018) in WMHs patients compared with healthy controls. In subgroup analyses, there was also a significant reduction of GABA+ levels in moderate-severe WMHs subgroup (p = 0.037) and mild WMHs subgroup (p = 0.047) when compared to HCs. Besides, the moderate-severe WMHs subgroup had significantly higher levels of tCho compared with healthy controls (p = 0.019). In conclusion, reduced GABA+ levels in WMHs patients and elevated tCho levels in moderate-severe WMHs were observed when compared with HCs. These results demonstrate that abnormalities of the GABAergic system and choline metabolism may contribute to the pathogenesis of WMHs.

Spectroscopic abnormalities in the pregenual anterior cingulate cortex in obsessive-compulsive disorder using proton magnetic resonance spectroscopy: a controlled study

BackgroundThe main aim of the present study is to determine the role of metabolites observed using proton magnetic resonance spectroscopy (1H-MRS) in obsessive-compulsive disorder (OCD). As the literature describing biochemical changes in OCD yields conflicting results, we focused on accurate metabolite quantification of total N-acetyl aspartate (tNAA), total creatine (tCr), total choline-containing compounds (tCh), and myo-inositol (mI) in the anterior cingulate cortex (ACC) to capture the small metabolic changes between OCD patients and controls and between OCD patients with and without medication.MethodsIn total 46 patients with OCD and 46 healthy controls (HC) matched for age and sex were included in the study. The severity of symptoms in the OCD was evaluated on the day of magnetic resonance imaging (MRI) using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Subjects underwent 1H-MRS from the pregenual ACC (pgACC) region to calculate concentrations of tNAA, tCr, tCho, and mI. Twenty-eight OCD and 28 HC subjects were included in the statistical analysis. We compared differences between groups for all selected metabolites and in OCD patients we analyzed the relationship between metabolite levels and symptom severity, medication status, age, and the duration of illness.ResultsSignificant decreases in tCr (U = 253.00, p = 0.022) and mI (U = 197.00, p = 0.001) in the pgACC were observed in the OCD group. No statistically significant differences were found in tNAA and tCho levels; however, tCho revealed a trend towards lower concentrations in OCD patients (U = 278.00, p = 0.062). Metabolic concentrations showed no significant correlations with the age and duration of illness. The correlation statistics found a significant negative correlation between tCr levels and YBOCS compulsions subscale (cor = -0.380, p = 0.046). tCho and YBOCS compulsions subscale showed a trend towards a negative correlation (cor = -0.351, p = 0.067). Analysis of subgroups with or without medication showed no differences.ConclusionsPatients with OCD present metabolic disruption in the pgACC. The decrease in tCr shows an important relationship with OCD symptomatology. tCr as a marker of cerebral bioenergetics may also be considered as a biomarker of the severity of compulsions. The study failed to prove that metabolic changes correlate with the medication status or the duration of illness. It seems that a disruption in the balance between these metabolites and their transmission may play a role in the pathophysiology of OCD.

Tiaogan Jiejiu Tongluo Formula attenuated alcohol-induced chronic liver injury by regulating lipid metabolism in rats

Ethnopharmacological relevanceTiaogan Jiejiu Tongluo Formula (TJTF), a traditional Chinese medicine formula, is modified from the well-known ancient prescription Danzhi-Xiaoyao Powder (DXP). Owing to its ability to regulate liver, strengthen spleen, detoxicating, and dredge collaterals in Chinese medicine, TJTF is usually used to treat anxiety, hypertension, alcoholic fatty liver disease in clinical application. However, the protective effect and potential molecular mechanism of TJTF on alcoholic liver injury has not fully been clarified. Aim of the studyTo explore the effect of TJTF on chronic alcoholic liver injury and figure out whether its effects were due to the regulation of lipid metabolism. Material and methods75 male SD rats were divided into the following five groups, control group, EtOH group, TJTF high dose group, TJTF low dose group and silybin group. Then a chronic alcoholic liver injury model was established by increasing concentration of 56% ethanol in rats. The rats in each TJTF group were given the corresponding dose of TJTF, the rats in the silybin group were given silybin, the rats in the control group and the EtOH group were given distilled water by gavage, once a day for 8 consecutive weeks. The components of TJTF were analyzed by UPLC-Q-TOF-MS. Hematoxylin and Eosin (H&E) was used to assess the severity of liver injury. in the pathological examination. Periodic acid-Schiff (PAS) and oil red O staining were used to evaluate the degree of the liver glycogen accumulation and lipid deposition, respectively. The serum ALT, AST, T-CHO, TG, LDL-C, ADH, HDL-C, and ALDH levels as well as liver tissue GSH, MDA, and SOD levels were analyzed in rats. Immunohistochemistry and western blotting were used to detect lipid metabolism-related proteins expressed in rat liver. ResultsTJTF significantly alleviated the chronic liver injury caused by alcohol in rats, and enhanced liver function. TJTF significantly decreased AST, ALT, ADH levels and increased ALDH level of serum, and increased GSH, SOD levels and decreased MDA level of liver tissue. In addition, TJTF significantly decreased the serum T-CHO, TG and LDL-C levels and increased HDL-C level in chronic alcoholic liver injury rats by regulating the expression of lipid metabolism associated proteins including p-LKB1, p-AMPKα, p-ACC, FAS, HMGCR, SREBP-1c, PPARα and CPT-1A. The results of western blot and immunohistochemical staining confirmed that TJTF can inhibit lipid production and promote fatty acid oxidation in the liver tissue of chronic alcoholic liver injury rats by activating the LKB1-AMPKα axis and then downregulating the protein expressions of p-ACC, FAS, HMGCR and SREBP-1c, as well as promoting the protein expressions of PPARα and CPT-1A. Meanwhile, TJTF also increased the glycogen content of liver and alleviated the liver damage. ConclusionAccording to current research, TJTF is effective in treating chronic liver damage induced by alcohol in rats. Additionally, TJTF exhibits the protective benefits by modulating LKB1-AMPKα signal axis, which in turn inhibits the synthesis of lipids and promotes the oxidation of fatty acids.

Effects of NUCB2/nesfatin-1 on lipid metabolism in the hepatopancreas of largemouth bass (Micropterus salmoides)

Although nucleobindin-2 (NUCB2)/nesfatin-1 has multiple biological functions, there is a scarcity of information regarding the regulatory effect of NUCB2/nesfatin-1 on lipid metabolism in mammals and fish. In order to investigate the mechanism underlying the effect of nesfatin-1 on lipid metabolism in largemouth bass (Micropterus salmoides), the sequence of NUCB2 was cloned and nesfatin-1 was expressed in prokaryotic system. Intraperitoneal injection of 5, 50 or 500 ng/g nesfatin-1 protein to determine differentially expressed genes (DEGs) in largemouth bass by transcriptomic profiling. The triglyceride and total cholesterol levels in the hepatopancreas and plasma were subsequently determined. The results showed that the NUCB2 cDNA sequence was 2015 bp in length and analyzed that NUCB2 mRNA was abundantly expressed in the hepatopancreas. RNA-seq analysis revealed that 385, 1647, and 750 genes were differentially expressed in the three groups, respectively, of which 33, 69, and 61 DEGs, respectively, were involved in lipid metabolism. GO and KEGG analysis showed that the DEGs were enriched in 24 signaling pathways related to lipid metabolism. The PPAR signaling pathway was significantly enriched following treatment with nesfatin-1. The fatty acid transport genes (ACSL, FABP3, FATP, ACBP) were significantly downregulated in the pathway (p < 0.05). Additionally, the TG (p < 0.01) and T-CHO (p < 0.05) levels in the hepatopancreas were significantly down-regulated at 50 ng/g nesfatin-1 protein injection dose, while TG and T-CHO levels in plasma were not significantly altered (p > 0.05). The present study demonstrated that at an optimal concentration, nesfatin-1 affected lipid metabolism in the hepatopancreas of largemouth bass primarily via the PPAR signaling pathway, to down-regulate the expression of fatty acid transport genes, which in turn decreased lipid synthesis in the hepatopancreas. The findings provide useful insights for further analysis of the mechanism underlying the effect of nesfatin-1, and for elucidating the regulation of lipid metabolism homeostasis in the aquaculture production of largemouth bass.

Systemic inflammation and cortical neurochemistry in never-medicated first episode-psychosis individuals

Studies of cellular and cytokine profiles have contributed to the inflammation hypothesis of schizophrenia; however, precise markers of inflammatory dysfunction remain elusive. A number of proton magnetic resonance spectroscopy (1H-MRS) studies in patients with first-episode psychosis (FEP) have shown higher brain levels of metabolites such as glutamate, myo-inositol (mI) and choline-containing compounds (tCho), suggesting neuroinflammation. Here, we present peripheral inflammatory profiles in antipsychotic-naive FEP patients and age-and-sex matched healthy controls, as well as cortical glutamate, mI and tCho levels using 1H-MRS. Inflammatory profiles were analyzed using cytokine production by peripheral blood mononuclear cells, that were either spontaneous or stimulated, in 48 FEP patients and 23 controls. 1H-MRS of the medial prefrontal cortex was obtained in 29 FEP patients and 18 controls. Finally, 16 FEP patients were rescanned after 4 weeks of treatment (open-label) with Risperidone. FEP patients showed a higher proportion of proinflammatory Th1/Th17 subset, and an increased spontaneous production of Interleukin (IL)-6, IL-2 and IL-4 compared with the control group. Results obtained from 1H-MRS showed no significant difference in either glutamate, mI or tCho between FEP and control groups. At baseline, CD8% showed a negative correlation with glutamate in FEP patients; after 4 weeks of risperidone treatment, the FEP group exhibited a decrease in glutamate levels which positively correlated with CD4 + T cells. Nevertheless, these correlations did not survive correction for multiple comparisons. FEP patients show evidence of immune dysregulation, affecting both the innate and adaptive immune response, with a predominantly Th2 signature. These findings, along with the changes produced by antipsychotic treatment, could be associated with both systemic and central inflammatory processes in schizophrenia.

Cordycepin reprogramming lipid metabolism to block metastasis and EMT via ERO1A/mTOR/SREBP1 axis in cholangiocarcinoma

Cholangiocarcinoma (CCA) with a high malignancy is usually diagnosed as advanced and is prone to metastasis and leads to a poor prognosis. It is reported that cordycepin has anti-tumor effect. However, the molecular targets and mechanisms of cordycepin in inhibiting CCA metastasis remains unclear. In order to evaluate the therapeutic effect of cordycepin on CCA metastasis, experiments were conducted in vivo and in vitro. The results showed that cordycepin inhibited the migration and EMT progression of HuCCT1 and QBC939 cells. Cordycepin has a strong hypolipidemic effects, therefore, we examined its effect on lipid metabolism in CCA. Cordycepin inhibits SREBP1 mediated fatty acid synthesis through the AKT/mTOR signaling pathway. Meanwhile, cordycepin can reduce ERO1A expression in HuCCT1 and QBC939 cells. ERO1A plays a role in malignant tumors. ERO1A promotes migration and lipid metabolism of CCA cells through AKT/mTOR signaling pathway. In addition, cordycepin significantly inhibited the tumor metastasis and the serum levels of TG and T-CHO in mice. Taken together, we demonstrate that cordycepin mediated ERO1A/mTOR/SREBP1 axis inhibits lipid metabolism and metastasis in CCA cells in vitro and in vivo. These data suggest that cordycepin can be used as a novel drug for the clinical treatment of CCA and to improve the prognosis.

Whole-brain MR spectroscopic imaging reveals regional metabolite abnormalities in perinatally HIV infected young adults.

Perinatally acquired HIV (PHIV) has been associated with brain structural and functional deficiencies, and with poorer cognitive performance despite the advent of antiretroviral therapy (ART). However, investigation of brain metabolite levels in PHIV measured by proton magnetic resonance spectroscopy (MRS) methods, is still limited with often inconclusive or contradictory findings. In general, these MRS-based methods have used a single voxel approach that can only evaluate metabolite concentrations in a few select brain anatomical regions. Additionally, most of the published data have been on children perinatally infected with HIV with only a few studies examining adult populations, though not exclusively. Therefore, this prospective and cross-sectional study aims to evaluate metabolite differences at the whole-brain level, using a unique whole-brain proton magnetic resonance spectroscopy imaging (MRSI) method, in a group of PHIV infected young adults (N = 28) compared to age and gender matched control sample (N = 28), and to find associations with HIV clinical factors and neurocognitive scores. MRSI data were acquired on a 3T scanner with a TE of 70 ms. Brain metabolites levels of total N-acetylaspartate (tNAA), total choline (tCho) and total creatine (tCre), as well as ratios of tNAA/tCre, tCho/tCre, and tNAA/tCho, were obtained from the whole brain level and evaluated at the level of gray matter (GM) and white matter (WM) tissue types and anatomical regions of interest (ROI). Our results indicate extensive metabolic abnormalities throughout the brains of PHIV infected subjects with significantly elevated levels of tCre and tCho, notably in GM regions. Decreases in tNAA and ratios of tNAA/tCre and tNAA/tCho were also found mostly in WM regions. These metabolic alterations indicate increased glial activation, inflammation, neuronal dysfunction, and energy metabolism in PHIV infected individuals, which correlated with a reduction in CD4 cell count, and lower cognitive scores. Our findings suggest that significant brain metabolite alterations and associated neurological complications persist in the brains of those with PHIV on long-term ART, and advocates the need for continued monitoring of their brain health.

1H-MRS of the anterior cingulate cortex in obsessive-compulsive disorder: metabolic abnormalities in pgACC - controlled study

IntroductionObsessive-compulsive disorder (OCD) is connected with increased activity in cortico-striatal-thalamic-cortical (CSTC) loop. The anterior cingulate cortex (ACC) is a part of this loop and plays a role in error detection and monitoring and processing of conflicting information, core OCD clinical signs. This area also contains a high density of Von Economo neurons. Biochemistry in this area is closely connected with the pathophysiology of OCD.ObjectivesDecreased concentrations of total N-acetylaspartate (tNAA) have been reported in ACC in patients with OCD compared to healthy controls (HC), with increase after successful treatment. Findings by other metabolites: choline-containing compounds (tCho), total creatine (tCr) and myo-inositol are not consistent. Differences in levels of tNAA, tCho, tCr would correlate with the severity of symptoms measured by Y-BOCS. In the comparison in the subgroup of patients with/ without medication, there will be differences in levels of metabolites.Methods54 patients diagnosed with OCD according to ICD-10 and DSM-IV criteria, and 54 HC matched for age and sex were included in the study. They underwent MRI and MR Spectroscopy on a 3T Magnetom Prisma scanner (Siemens, Germany) equipped with a 64-channel volume head coil (Fig. 2). After spectral quality control, 28 OCD and 28 HC subjects were included in the statistical analysis. OCD subjects were interviewed using the Y-BOCS to evaluate the severity of the symptoms. Patients enrolled in the study were without medication at least 5 days before MRI or on a stable dosage of SSRI antidepressants. To assess the intergroup differences Wilcoxon Rank Sum test or Kruskal-Wallis test was used as appropriate. The correlation between metabolite levels and clinical characteristics was assessed by Spearman’s rank correlation coefficient. The statistics were calculated using R, version 4.1.1.ResultsWe found no differences in levels of tNAA in ACC in OCD vs. HC (p=0,21; see Tab.1, Fig.1). We found significantly increased level of tCho, tCr and Ins in OCD vs. HC (p=0,03; p=0,004 resp.; p=0,017 resp.). tCr levels corelated negatively with YBOCS compulsions subscale (p=0,046; cor=-0,38). tCho levels showed a trend to negative correlation with Y-BOCS compulsions subscale (p=0,067; cor=-0,35). Analysis on the subgroup with (13 subjects, 46,43 %) and without (13 subjects, 46,43 %) stable SSRI medication did not reveal significant differences.Image:Image 2:ConclusionsOur study found difference in ACC by OCD patients compared to HC, mainly increased tCho, tCr and Ins. Also, the study shows a significant correlation between the severity of compulsions and tCr levels. We can see this trend also in the correlation of the tCho and Y-BOCS compulsions subscale. Similar tNAA level by OCD and HC groups could indicates correctly adjusted medication or stable state by enrolled patients.Disclosure of InterestNone Declared

Hippocampal Metabolic Alterations in Amyotrophic Lateral Sclerosis: A Magnetic Resonance Spectroscopy Study

Magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) has been overwhelmingly applied to motor regions to date and our understanding of frontotemporal metabolic signatures is relatively limited. The association between metabolic alterations and cognitive performance in also poorly characterised. In a multimodal, prospective pilot study, the structural, metabolic, and diffusivity profile of the hippocampus was systematically evaluated in patients with ALS. Patients underwent careful clinical and neurocognitive assessments. All patients were non-demented and exhibited normal memory performance. 1H-MRS spectra of the right and left hippocampi were acquired at 3.0T to determine the concentration of a panel of metabolites. The imaging protocol also included high-resolution T1-weighted structural imaging for subsequent hippocampal grey matter (GM) analyses and diffusion tensor imaging (DTI) for the tractographic evaluation of the integrity of the hippocampal perforant pathway zone (PPZ). ALS patients exhibited higher hippocampal tNAA, tNAA/tCr and tCho bilaterally, despite the absence of volumetric and PPZ diffusivity differences between the two groups. Furthermore, superior memory performance was associated with higher hippocampal tNAA/tCr bilaterally. Both longer symptom duration and greater functional disability correlated with higher tCho levels. Hippocampal 1H-MRS may not only contribute to a better academic understanding of extra-motor disease burden in ALS, but given its sensitive correlations with validated clinical metrics, it may serve as practical biomarker for future clinical and clinical trial applications. Neuroimaging protocols in ALS should incorporate MRS in addition to standard structural, functional, and diffusion sequences.

The Prognostic Implications of Perioperative Serum Cholesterol Levels in Patients With Gastric Cancer.

Although cholesterol is an important indicator of nutritional status, it is also involved in cancer progression. In this study, we investigated the clinical significance of the dynamics of perioperative total cholesterol (T-Cho) levels in patients with gastric cancer (GC). A total of 212 patients with pathological stage II/III disease who underwent gastrectomy between 2004 and 2020 were enrolled in this retrospective study. The preoperative and postoperative serum T-Cho levels were measured in these patients. Increased serum T-Cho levels were significantly correlated with low preoperative serum albumin levels (p<0.001). Patients with increased serum T-Cho levels after surgery had significantly lower overall and recurrence-free survival rates (p=0.030 and p=0.013, respectively; log-rank test). Cox proportional hazards model revealed that increased serum T-Cho levels (p=0.040), advanced pathological stage (p<0.001), and the provision of adjuvant chemotherapy (p=0.006) were independent prognostic factors for recurrence-free survival in patients with GC. Increased serum T-Cho levels after gastrectomy may be an independent prognostic factor in patients with GC.

N-methylformamide induces multiple organ toxicity in Fischer 344 rats.

N-Methylformamide (NMF) is a widely used chemical (CAS No.: 123-39-7) in several industries and its usage is continuously increasing. However, studies for NMF have been focused on hepatotoxicity from now. Its toxicity profile has not yet been established owing to limited toxicity data. Therefore, we evaluated systemic toxicity via NMF inhalation. We exposed 0, 30, 100, and 300ppm NMF to Fischer 344 rats for 6h/day, 5days a week for 2weeks. Clinical signs, body weights, food consumption, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathology were performed. Two females exposed to 300ppm NMF died during exposure period. Decrease of food consumption and body weight in both sexes exposed to 300ppm in females exposed to 100ppm were noted during exposure period. Increased RBC and HGB were noted in females exposed to 300ppm. A decrease in the levels of ALP and K and increase in the levels of TCHO and Na were observed in both sexes exposed to 300 and 100ppm. Increased levels of ALT, AST, BUN and decreased levels of TP, ALB, Ca were observed in females exposed to 300 and 100ppm. The relative liver weight was elevated in both sexes exposed to 300 and 100ppm NMF. Hypertrophy in the liver and submandibular glands and nasal cavity injuries were noted in both sexes exposed to 300 and 100ppm NMF. Tubular basophilia of the kidneys were noted in females exposed to 300ppm NMF. We revealed that NMF affect several organs including the kidneys not only the liver and NMF-related toxicity is predominant in female rats. These results could contribute to the development of NMF toxicity profile and may help in developing strategies for the control of occupational environmental hazards related to NMF.

Altered neurometabolite levels in the brains of patients with depression: A systematic analysis of magnetic resonance spectroscopy studies

BackgroundNumerous magnetic resonance spectroscopy (MRS) studies have reported metabolic abnormalities in the brains of patients with depression, although inconsistent results have been reported. The aim of this study was to explore changes in neurometabolite levels in patients with depression across large-scale MRS studies. MethodA total of 307 differential metabolite entries associated with depression were retrieved from 180 MRS studies retrieved from the Metabolite Network of Depression Database. The vote-counting method was used to identify consistently altered metabolites in the whole brain and specific brain regions of patients with depression. ResultsOnly few differential neurometabolites showed a stable change trend. The levels of total choline (tCho) and the tCho/N-acetyl aspartate (NAA) ratio were consistently higher in the brains of patients with depression, and that the levels of NAA, glutamate and glutamine (Glx), and gamma-aminobutyric acid (GABA) were lower. For specific brain regions, we found lower Glx levels in the prefrontal cortex and lower GABA concentrations in the occipital cortex. We also found lower concentrations of NAA in the anterior cingulate cortex and prefrontal cortex. The levels of tCho were higher in the prefrontal cortex and putamen. ConclusionOur results revealed that most altered neurometabolites in previous studies lack of adequate reproducibility. Through vote-counting method with large-scale studies, downregulation of glutamatergic neurometabolites, impaired neuronal integrity, and disturbed membrane metabolism were found in the pathobiology of depression, which contribute to existing knowledge of neurometabolic changes in depression. Further studies based on a larger dataset are needed to confirm our findings.

Role of neurochemistry in amyloid pathology using 5xFAD transgenic mouse model of AD: A single‐voxel Magnetic Resonance Spectroscopy (MRS) study

AbstractBackgroundChanges in cerebral metabolic concentrations are markers of aging and are also associated with various neurological disorders. Neurotransmitter and membrane metabolisms are affected in Alzheimer’s disease (AD). These metabolic alterations are suggested to occur in the hippocampus and rhinal cortex during the early stages of AD pathology. Higher levels of glutamine (Gln) in the blood and cerebral spinal fluid are associated with an increased risk of developing AD. Since Gln is capable of crossing the blood‐brain barrier and is involved in the metabolic cycle with glutamate (Glu), elevated levels of Gln in the presence of Aβ pathology may suggest a protective role of Gln in the early stage of the disease. Therefore, alteration in Glu/Gln cycle may serve as an early biomarker in the pathogenesis of AD. Choline‐containing compounds (tCho) are essential for phospholipid synthesis and degradation of cell membranes. Abnormal alterations of tCho levels are indicative of imbalanced cell membrane phospholipid metabolism. At the early stage of Aβ pathology, high levels of tCho in conjunction with elevated levels of Gln may suggest the involvement of compensatory mechanisms to counter declining acetylcholine. Thus, investigating metabolic changes in the hippocampus may improve our understanding of metabolic mechanisms associated with Aβ pathology.MethodMale 5xFAD mice (N=4) at 6‐months‐old and age‐matched littermates (N=5) were used in this study. Single‐voxel MRS was acquired on a 9.4T Biospec micro‐MRI system equipped with a H1 cryogenic surface coil. STEAM spectra was acquired from a 2mm3 voxel positioned on the left hippocampus region. Glu, Gln, tCho and total Creatine (tCr) levels were estimated with LC Model. A general linear model (GLM) was used to estimate group‐wise differences in Glu/Gln ratio, tCho.Gln and tCr.ResultCerebral metabolic concentration levels suggest group‐level differences between wild‐type (WT) and 5xFAD mice. Glu/Gln ratio was significantly higher in WT mice than 5xFAD (pFWE&lt;0.05; d=3.4) and tCho.Gln was significantly lower in WT than 5xFAD (pFWE&lt;0.05; d=2.8).ConclusionSingle‐voxel MRS in the hippocampus region can identify the neurochemical profile of multiple cerebral metabolites, which may be sensitive to the Aβ burden at the early stages of the pathology.

Nutritional and Cytogenetic Assessment Predicts Favorable Response to Azacitidine Monotherapy for Myelodysplastic Syndromes

High-risk myelodysplastic syndrome (HR-MDS) has a poor outcome, and not many patients can benefit from the standard of care with azacitidine (AZA) monotherapy. The main reasons for the poor prognosis include transformation to acute myeloblastic leukemia (AML), adverse events, such as infection, and intolerance to therapy. The transformation to AML is frequently associated with features of cytogenetic abnormalities, while the patients' conditions, like nutritional status and frailty, influence the emergence of infectious complications and therapeutic intolerance. In addition, the importance of the nutritional assessment has been reported in other cancers, and albumin, total cholesterol (T-Cho), and body weight have been often used as nutritional parameters. However, the conventional prognostic indices for MDS, such as the International Prognostic Scoring System (IPSS-R) and Revised IPSS (IPSS-R), do not include those factors. In this study, we tried to develop a novel prognostic tool by reassessing the prognostic values of pre-existing prognostic factors with nutritional assessment in patients with MDS treated by AZA. One hundred six patients who started AZA monotherapy between 2011 January and 2021 December at four independent institutes (University Hospital Kyoto Prefectural University of medicine, Fukuchiyama City Hospital, Aiseikai Yamashina Hospital, and Kyoto Kuramaguchi Medical Center), belonging to the Kyoto Clinical Hematology Study Group were retrospectively analyzed by collecting clinical and survival data using case report forms. Data collected include factors involved in IPSS-R score (absolute neutrophil count (ANC), hemoglobin level (Hb), platelets (Plt), rate of bone marrow (BM) blasts and karyotype), serum levels of albumin and T-Cho, age, gender, and body mass index (BMI). Overall survival (OS) was defined as the time from the initiation date of AZA treatment to death from any cause or the date of the last follow-up, and was estimated using the Kaplan Meier method. Females were 26 (24.5%) and the median age was 73 years (31-92). According to IPSS-R, 54 (50.9%) patients were classified as very high, 31 (29.2%) as high, 18 (17.0%) as intermediate, and 3 (2.8%) as low. With the median follow-up period of 8.7 months (0.6-55.0), the median OS of the entire cohort was 10.2 months (95% confidence interval (CI), 8.8-12.8). By the univariate analysis by Cox proportional hazard analyses for OS, we identified T-Cho, Hb, albumin, and cytogenetic risk defined by IPSS-R as poor prognostic factors with the cutoff p-value of 0.1. By the multivariate analysis using these factors as variables, T-Cho and CR were found to be significantly associated with poor prognosis in our cohort (p-value; 0.013 and 0.006, respectively). Accordingly, we divided patients into two groups, i.e., a group of patients with good nutritional status and low cytogenetic risk and the other group of patients with poor nutritional status and/or high cytogenetic risk, and we here designated this classification as the nutritional and cytogenetic classification (NCC). With this classification, T-Cho< 150 mg/dL was considered to be indicative of poor nutrition, while the high cytogenetic risk was defined as very poor in IPSS-R. In NCC, 24 patients (22.6%) were classified as a good-nutritional/low cytogenetic risk group, while others were as a poor nutritional/high cytogenetic risk group. As the result, the median OS of the former was 26.1 months (95% CI, 21.34-44.0), while that of the latter was 8.9 months (95% CI, 6.6-10.8) (p <0.001, log-rank test). In addition, the former group was significantly associated with higher Hb. The C-indices of IPSS-R and NCC were 0.595 (standard error (SE); 0.033) and 0.611 (SE; 0.027), respectively, showing a more favorable risk discrimination ability of NCC than IPSS-R in our cohort. In conclusion, we here propose a new prognostic model, designated as NCC, for patients with MDS treated by AZA monotherapy, which, incorporates the serum level of T-Cho as a prognostic factor in addition to the cytogenetic risk, of which C-index was higher than the conventional IPSS-R. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Lactobacillus reuteri MJM60668 Prevent Progression of Non-Alcoholic Fatty Liver Disease through Anti-Adipogenesis and Anti-inflammatory Pathway.

Non-alcoholic fatty liver disease (NALFD) is a disease characterized by liver steatosis. The liver is a key organ involved in the metabolism of fat, protein, and carbohydrate, enzyme activation, and storage of glycogen, which is closely related to the intestine by the bidirectional relation of the gut-liver axis. Abnormal intestinal microbiota composition can affect energy metabolism and lipogenesis. In this experiment, we investigated the beneficial effect of Lactobacillus reuteri MJM60668 on lipid metabolism and lipogenesis. C57BL/6 mice were fed a high-fat diet (HFD) and orally administrated with MJM60668. Our results showed that mice treated with MJM60668 significantly decreased liver weight and liver/body weight ratio, without affecting food intake. Serum levels of ALT, AST, TG, TCHO, and IL-1β in mice fed with MJM60668 were decreased compared to the HFD group. Investigation of gene and protein expression on the lipogenesis and lipid metabolism showed that the expression of ACC, FAS, and SREBP was decreased, and PPARα and CPT was increased. Furthermore, an increase of adiponectin in serum was shown in our experiment. Moreover, serum IL-1β level was also significantly decreased in the treated mice. These results suggested that MJM60668 can strongly inhibit lipogenesis, enhance fatty acid oxidation, and suppress inflammation. Additionally, supplementation of MJM60668 increased the proportion of Akkermansiaceae and Lachnospiracea, confirming a potential improvement of gut microbiota, which is related to mucus barrier and decrease of triglycerides levels.

Oral administration of human FGF21 expressed by mycelium of Cordyceps militaris improves blood glucose and lipid in type II diabetes mellitus.

The purpose of this study was to express human FGF21 (hFGF21) using Cordyceps militaris (C. militaris) as a bioreactor and to observe its hypoglycemic and lipid-lowering effects on type II diabetes. The recombinant plasmid pCB130-hFGF21 was transformed into C. militaris to form recombinant recombinant C. militaris (RhFGF21), the stability of RhFGF21 in vitro and in vivo was analyzed. RhFGF21 significantly promoted glucose uptake in a dose-dependent manner in adipocytes and increased the levels of p-PLCγ, p-FRS2 and p-ERK, which was consistent with the commercial hFGF21. In animal experiments, oral RhFGF21 obviously reduced the levels of glucose, insulin, TG, T-CHO, NEFA, and LDL-C in the blood, the contents of ALT, AST, TNF-α, MCP-1, F4/80, CD68 and CD11b in the fatty liver, and the apoptosis of pancreatic cells. C. militaris is an excellent carrier that can stabilize the expression of hFGF21 and protect the biological activity of hFGF21 during oral administration, which provides a theoretical basis for the development of hFGF21 oral preparations for type II diabetes.

Effect of PCI Standardized Telephone Follow-Up Service Mode on Out-of-Hospital Complications, Rehospitalization Rate, and Quality of Life of Discharged Patients with Acute Coronary Syndrome after PCI.

Objective To explore the effect of percutaneous coronary intervention (PCI) standardized telephone follow-up service mode on out-of-hospital complications, rehospitalization rate, and life quality of discharged acute coronary syndrome (ACS) patients after PCI. Methods From August 2020 to March 2022, 218 ACS patients who were discharged after PCI were included. The controls accepted routine nursing care, and the researches accepted PCI standardized telephone follow-up service mode. The nursing satisfaction, rehospitalization rate, out-of-hospital complication rate, blood lipid level, and life quality score were taken as the comparisons. Results The nursing satisfaction of study group (100.00%) was significantly higher than that of control group (88.07%). The rehospitalization rate was dramatically lower in the study group (3/109; 2.75%) than in the control group (25/109; 22.94%) (P < 0.05). In addition, compared with the control group, the incidence of complications (acute myocardial infarction and angina pectoris) was significantly reduced in the study group outside the hospital (P < 0.05). The blood lipid levels of TCHO, TG, LDL-C, and HDL-C were lower in the study group than in the controls. Further, after nursing, the quality of life score of the two groups was both decreased with a higher quality of life score in the study group (P < 0.05). Conclusion The application of PCI standardized telephone follow-up service mode in discharged patients with acute coronary syndrome after PCI can reduce out-of-hospital complications and rehospitalization rate and improve blood lipid level and life quality.